Novel function of vitamin E in regulation of zebrafish (Danio rerio) brain lysophospholipids discovered using lipidomics

J Lipid Res. 2015 Jun;56(6):1182-90. doi: 10.1194/jlr.M058941. Epub 2015 Apr 8.


We hypothesized that brains from vitamin E-deficient (E-) zebrafish (Danio rerio) would undergo increased lipid peroxidation because they contain highly polyunsaturated fatty acids, thus susceptible lipids could be identified. Brains from zebrafish fed for 9 months defined diets without (E-) or with (E+) added vitamin E (500 mg RRR-α-tocopheryl acetate per kilogram diet) were studied. Using an untargeted approach, 1-hexadecanoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine [DHA-PC 38:6, PC 16:0/22:6]was the lipid that showed the most significant and greatest fold-differences between groups. DHA-PC concentrations were approximately 1/3 lower in E- (4.3 ± 0.6 mg/g) compared with E+ brains (6.5 ± 0.9 mg/g, mean ± SEM, n = 10 per group, P = 0.04). Using lipidomics, 155 lipids in brain extracts were identified. Only four phospholipids (PLs) were different (P < 0.05) between groups; they were lower in E- brains and contained DHA with DHA-PC 38:6 at the highest abundances. Moreover, hydroxy-DHA-PC 38:6 was increased in E- brains (P = 0.0341) supporting the hypothesis of DHA peroxidation. More striking was the depletion in E- brains of nearly 60% of 19 different lysophospholipids (lysoPLs) (combined P = 0.0003), which are critical for membrane PL remodeling. Thus, E- brains contained fewer DHA-PLs, more hydroxy-DHA-PCs, and fewer lysoPLs, suggesting that lipid peroxidation depletes membrane DHA-PC and homeostatic mechanisms to repair the damage resulting in lysoPL depletion.

Keywords: 1-hexadecanoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine; Land’s cycle; α-tocopherol.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain / metabolism
  • Fatty Acids / metabolism
  • Lipid Peroxidation*
  • Lipids / biosynthesis*
  • Lipids / isolation & purification
  • Lysophospholipids / isolation & purification
  • Lysophospholipids / metabolism*
  • Vitamin E / administration & dosage
  • Vitamin E / metabolism*
  • Vitamin E Deficiency / genetics
  • Vitamin E Deficiency / metabolism
  • Zebrafish / metabolism


  • Fatty Acids
  • Lipids
  • Lysophospholipids
  • Vitamin E
  • lysophosphatidic acid